Naval support ship Wave Knight provided vital back-up as the US Coast Guard boarded a suspect speedboat.
Warning shots were fired as the two-man crew tried to jettison their cargo, forcing the motorboat to a standstill.
Packages weighing a total of 170kg later tested positive for cocaine and the two men were transferred to mainland US.
The Royal Fleet Auxiliary (RFA) ship's latest success comes hot on the heels of its role in a 1,250kg cocaine bust last month south of the Dominican Republic.
It is deployed as part of Operation Martillo, a 15-nation joint effort to disrupt drug trafficking from Central and South America into the Caribbean and onwards to the UK.
Captain Duncan Lamb, RFA Wave Knight's commanding officer, said: "RFA Wave Knight's latest cocaine seizure rounds off a very successful patrol and underlines the effectiveness of multi-national counter narcotics operations in the Caribbean.
"The ship, US Coast Guard law enforcement detachment and an armed US Coast Guard helicopter working together present a formidable obstacle to the smugglers."
Armed with Vulcan Phalanx Gatling guns, self-defence weapons and decoys, the 31,500 tonne fleet tanker provides a launchpad for helicopters at sea.
It also has the capacity to refuel and resupply other naval vessels.
The RFA is a flotilla of 13 naval support ships that delivers afloat support to UK and Allied armed forces around the world.
Owned by the Ministry of Defence, it is manned by British civilian sailors who are trained to operate alongside the Royal Navy.